Cancer is a class of diseases in which a group of cells exhibit uncontrolled growth, invasion and destruction of adjacent tissues, and metastasis (the spread of aberrant cells to other locations in the body), or in which cells fail to undergo programmed cell death (e.g. apoptosis) at the appropriate time. Cancer causes about 13% of all deaths worldwide. Current treatments for cancer depend upon the specific type of cancer and tissue involved, but include surgery, chemotherapy, radiation therapy, immunotherapy, and monoclonal antibody therapy among other methods. Although these treatment methods have been successful in some cases, they are hindered by adverse side effects or limited efficacy. For example, the efficacy of eliminating cancerous tissue by surgical removal of tumors is often limited by the tendency of cancers to invade adjacent tissue and metastasize to other sites in the body. Chemotherapy, as well as radiation treatment, is often limited by toxicity or damage to other tissues in the body. Thus, cancer remains a major health concern and there is a need for improved methods of diagnosing and treating cancer.
Diagnosis of cancer can occur at any stage of disease. In many cases, determination of an appropriate course of treatment, which may include invasive surgery or administration of toxic drugs, is postponed until disease progression is observed so that the severity of disease can be determined and the appropriate therapeutic course can be selected. Systems that would allow clinicians to rapidly determine whether a patient would benefit from aggressive treatment or whether a less aggressive form of treatment is appropriate would drastically improve the treatment of individuals with cancer.
Of the nearly 84,000 annual cases of leukemia in the Western world, B-cell CLL is the most common, accounting for ˜30% of adult leukemia cases. (Ishibe el al. 2001) Characterized by accumulation of monoclonal mature B cells (Rozman et al. 1995), the CLL clinical course is heterogeneous, with some patients experiencing an aggressive course that demands early treatment, and others experiencing long survival without disease-related symptoms or ever requiring treatment. (Rozman et al. 1995) Aberrant apoptosis in CLL cells correlates with arrest either in the G0 or early G1 phases of the cell cycle. (Cordone et al. 1992) (Caligaris-Cappio et al. 1999) This defective apoptosis in CLL cells is partly due to aberrant signaling through the Akt kinase and the ERK mitogen activated protein kinase (MAPK) pathways, in which phosphorylated-Akt (p-Akt) is necessary for survival of the leukemia cells. (Cuni et al. 2004) (Longo et al. 2008) The observation of aberrantly activated Akt and downstream pathways in CLL cells also suggests that the normal regulator of these pathways, PP2A, is unable to perform its normal role.
Non-Hodgkin's lymphoma is a lymphoma characterized by malignant growth of B lymphocytes. Many non-Hodgkin's lymphoma patients have intermediate- or high-grade disease, which are much more aggressive at the time of diagnosis than low-grade disease. The distinction among the grades of non-Hodgkin's lymphoma is important and can have a strong impact on the treatment regimen selected for the patient. Patients with low-grade non-Hodgkin's lymphoma may survive an average of 5-7 years with conventional therapies, whereas patients with intermediate or high grade non-Hodgkins lymphoma have an average survival rate of 2-5 years or 6 months to 2 years, respectively.
There is a need in the art for methods of predicting the level of severity of cancers or linking the progression of cancers with particular markers. In addition, means for making rapid determinations with regard to such markers in clinical diagnostic labs are also needed. The present invention addresses these and other needs.